Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2.
Although in different groups, the coronaviruses severe acute respiratory syndrome-coronavirus (SARS-CoV) and NL63 use the same receptor, angiotensin converting enzyme (ACE)-2, for entry into the host cell. Despite this common receptor, the consequence of entry is very different; severe respiratory distress in the case of SARS-CoV but frequently only a mild respiratory infection for NL63. Using a wholly recombinant system, we have investigated the ability of each virus receptor-binding protein, spike or S protein, to bind to ACE-2 in solution and on the cell surface. In both assays, we find that the NL63 S protein has a weaker interaction with ACE-2 than the SARS-CoV S protein, particularly in solution binding, but the residues required for contact are similar. We also confirm that the ACE-2-binding site of NL63 S lies between residues 190 and 739. A lower-affinity interaction with ACE-2 might partly explain the different pathological consequences of infection by SARS-CoV and NL63.
Mathewson
Alison C
AC
School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK.
Bishop
Alexandra
A
School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK.
Yao
Yongxiu
Y
School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK.
Kemp
Fred
F
School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK.
Ren
Junyuan
J
School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK.
Chen
Hongying
H
School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK.
Xu
Xiaodong
X
School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK.
Berkhout
Ben
B
Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, K3-110, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
van der Hoek
Lia
L
Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, K3-110, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Jones
Ian M
IM
School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK.
D000085962:Angiotensin-Converting Enzyme 2; D017934:Coronavirus / Q000502:physiology*; D018352:Coronavirus Infections / Q000503:physiopathology*; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011485:Protein Binding; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology*; D045169:Severe Acute Respiratory Syndrome / Q000503:physiopathology*; D012720:Severity of Illness Index; D012996:Solutions; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000378:metabolism*
D008562:Membrane Glycoproteins; D012996:Solutions; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2